Topical delivery of a Rho-kinase inhibitor to the cornea via mucoadhesive film

Abstract

The application of inhibitors of the Rho kinase pathway (ROCK inhibitors) to the surface of the eye in the form of eyedrops has beneficial effects which aid the recovery of diseased or injured endothelial cells that line the inner surface of the cornea. The aim of this study was to test the plausibility of delivering a selective ROCK inhibitor, Y-27632, to the cornea using a thin polymeric film. Mucoadhesive polymeric thin films were prepared incorporating Y-27632 and diffusional release into PBS was determined. Topical ocular delivery from the applied film was investigated using freshly excised porcine eyes and eyedrops of equivalent concentration acted as comparators; after 24h the formulations were removed and the corneas extracted. Drug-loaded thin polymeric films, with high clarity and pliability were produced. ROCK inhibitor Y-27632 was weakly retained within the film, with release attaining equilibrium after 1h. This in turn facilitated its rapid ocular delivery, and an approximately three-fold greater penetration of Y-27632 into cryoprobe-treated corneas was observed from the thin film (p<0.01) compared to eyedrops. These findings support the further development of ROCK inhibitor delivery to the cornea via release from thin mucoadhesive films to treat vision loss cause by corneal endothelial dysfunction.

Allogeneic Descemet's Membrane Transplantation Enhances Corneal Endothelial Monolayer Formation and Restores Functional Integrity Following Descemet's Stripping

“…If successful, it may be possible to exchange donor tissue for a tissueengineered DM substitute with modified mechanical and topographic profiles 47 similar to those of human DM. This could be further improved with modified surface chemistry or eluting drugs 50 designed to promote cell migration and proliferation.…”

A Surgical Cryoprobe for Targeted Transcorneal Freezing and Endothelial Cell Removal

“…It thus has the potential to rapidly and reliably induce damage to the human corneal endothelium via transcorneal freezing, leaving the epithelial basement membrane intact. This has the potential to be used prior to the application of ROCK inhibitors to the eye in the form of eye drops [10–12] or as slow-release chemicals from thin films [40] to aid the recovery of corneal endothelial function.…”

The Application of Rho Kinase Inhibitors in the Management of Glaucoma

“…AR-13503, a prodrug of netarsudil, has been investigated as a biodegradable sustained-release intravitreal implant in animal models [ 93 ], with ongoing clinical trials focusing on DME and neovascular age-related macular degeneration patients (NCT03835884). Other delivery systems have been proposed in animal studies, such as drug-loaded thin polymeric films for corneal endothelial dysfunction [ 94 ] and Y27632-PLGA-modified intraocular lenses, which can prevent posterior capsular opacification formation [ 95 ]. Overall, these drug delivery systems aim to enhance the efficacy and safety of ROCK inhibitors for treating various ocular diseases.…”